Indocyanine green, chemically known as sodium 4-[2-[(1E,3E,5E,7Z)-7-[1,1-dimethyl-3-(4-sulfonatobutyl)benzo[e]indol-2-ylidene]hepta-1,3,5-trienyl]-1,1-dimethylbenzo[e] indol-3-ium-3-yl]butane-1-sulfonate, used in medical diagnostics. It is used for determining cardiac output, hepatic function, and liver blood flow, and for ophthalmic angiography.
Indocyanine green is a fluorescent dye which is used in medicine as an indicator substance (e.g. for photometric hepatic function diagnostics and fluorescence angiography) in cardiac, circulatory, hepatic and ophthalmic conditions. It is administered intravenously and, depending on liver performance, is eliminated from the body with a half life of approx. 3-4 minutes. Indocyanine green sodium salt is normally available in powder form and can be dissolved in various solvents; 5% (<5% depending on batch) sodium iodide is usually added to ensure better solubility. The sterile lyophilisate of a water-Indocyanine green solution is approved many European countries and the United States under the names Indocyanine green-Pulsion and Indocyanine green as a diagnostic for intravenous use.
U.S. Pat. No. 2,895,955 describes a structure including Indocyanine green and its pharmaceutically acceptable salts. Indocyanine green as its pharmaceutical acceptable salts[iodide disodium salt]. In accordance with the US'955 patent, Indocyanine green can prepared by reacting 1,1,2-trimethyl-1H-benzo[e]indole with 1,4-butane sultone in without solvent to produce 4-(1,1,2-trimethyl-1H-benzo[e]indolium-3-yl)butane-1-sulfonate, followed by treatment with N-phenyl-N-((1E,3E,5E)-5-(phenylimino)penta-1,3-dienyl)acetamide triethyl amine in ethanol and extraction in ether, and making sodium iodide salt in alcoholic solvent. In this process 4-(1,1,2-trimethyl-1H-benzo[e]indolium-3-yl)butane-1-sulfonate compound is not isolating or not easy filtration, also Indocyanine green not getting purity 99.0%.
According to PCT application WO2014/165216 patent, intermediate of N-((1E,3E,5E)-5-(phenylimino)penta-1,3-dien-1-yl) benzenaminium chloride treated with acetic anhydride in presence of triethylamine at −20° C. to give N-phenyl-N-((1E,3E,5E)-5-(phenylimino)penta-1,3-dienyl)acetamide, reaction carried out concentrated under high vacuum.
According to PCT application WO 2014192972 patent, intermediate of N-((1E,3E,5E)-5-(phenylimino)penta-1,3-dien-1-yl) benzenaminium chloride treated with acetic anhydride in presence of sodium acetate at 100° C. to give N-phenyl-N-((1E,3E,5E)-5-(phenylimino)penta-1,3-dienyl)acetamide, reaction 4-(1,1,2-trimethyl-1H-benzo[e] indolium-3-yl)butane-1-sulfonate in water.
U.S. Pat. No. 5,750,722 disclosed a process for preparing Indocyanine green acetone as purification solvent. And also US20090069573 patent purification solvent is methylene dichloride.
Wang, Dun; Jin, Wenshu; Qin, Enwei; Wang, Shuobing; Li, Peng Zhongguo Yiyao Gongye Zazhi Volume 37, Issue 9, Pages 584-585(2006) process for making indocyanine green.
Kundu, Kousik; Knight, Sarah F.; Willett, Nick; Lee, Sungmun; Taylor, W. Robert; Murthy, Niren Angewandte Chemie, International Edition Volume 48, Issue 2, Pages 299-303(2009) disclosed process for making Hydrocyanines: a class of fluorescent sensors that can image reactive oxygen species in cell culture, tissue, and in vivo.
According to PCT application WO2007/120579 patent describe process for making Indocyanine green as sodium iodide salt.